Risk factors for post-hepatectomy liver failure in 80 patients.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is a serious complication and a leading cause of death after hepatectomy, an accurate prediction of PHLF is important for improvement of prognosis after hepatectomy. AIM: To retrospectively analyze the risk factors for postoperative liver failure in patients undergoing hepatectomy for liver tumors. METHODS: The clinical data of 80 patients undergoing hepatectomy in our hospital from June 2018 to January 2020 were collected. With laboratory examination as well as pre- and post-operative abdominal three-dimensional reconstructive computed tomography, the demographic data, surgical data, biochemical indicators, coagulation index, routine blood tests, spleen and liver volumes, relative remnant liver volume, and other related indicators were obtained and compared between patients with PHLF and those without PHLF. RESULTS: PHLF occurred in 19 (23.75%) patients. Univariate logistic regression analysis showed that gender, history of hepatitis/cirrhosis, and preoperative bilirubin, albumin, coagulation function, albumin-bilirubin ratio, aspartate amino-transferase-to-platelet ratio index (APRI), Model for End-Stage Liver Disease score, spleen volume (SV), spleen volume/liver volume ratio (SV/LV), and relative remnant liver volume were statistically associated with the occurrence of PHLF (all P < 0.05). Multivariate regression analysis showed that preoperative total bilirubin, platelets (PLT), APRI, and SV/LV were independent risk factors for PHLF (all P < 0.05). The area under the curve and cut-off values were 0.787 and 18.6 mmol/L for total bilirubin, 0.893 and 146 × 1012/L for PLT, 0.907 and 0.416 for APRI, and 0.752 and 20.84% for SV/LV, respectively. CONCLUSION: For patients undergoing liver resection, preoperative total bilirubin, PLT, APRI, and SV/LV are independent risk factors for PHLF. These findings may provide guidance to safely perform liver surgery in such patients.

Short-Term Outcomes of Self-Expandable Metallic Stent versus Decompression Tube for Malignant Colorectal Obstruction: A Meta-Analysis of Clinical Data.

Purpose: To compare the short-term outcomes between self-expandable metallic stent (SEMS) and decompression tubes (DT) for malignant colorectal obstruction. Methods: A comprehensive literature search was performed from inception to 2018/12/6 covering Pubmed, Embase, and Cochrane library. Methodological assessments of eligible studies were performed by using Newcastle-Ottawa Scale (NOS). The Revman software (version 5.3) was used in our statistical analysis. Results: Totally 7 cohort studies were enrolled in our meta-analysis. All the 7 eligible studies proved to be high quality according to the NOS scale. Patients receiving SEMS had higher clinical success rates, higher laparoscopic surgery rates, and higher primary anastomosis rates compared with patients receiving DT. Conclusions: Based on evidence from eastern countries, SEMS placement is an effective procedure that treats malignant colorectal obstruction. Compared with DT placement, patients receiving SEMS may benefit from higher clinical success rates, higher laparoscopic surgery rates, and higher primary anastomosis rates.

Is There Necessity for Oversewing the Staple Line During Laparoscopic Sleeve Gastrectomy? An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Laparoscopic sleeve gastrectomy (LSG) has become the current mainstream surgical treatment for obesity. With the development of clinical practice, surgeons realized the associated severity and danger of postoperative bleeding and leakage. Surgeons constantly explore different strategies to reduce the incidence of these complications. By reviewing previous clinical articles on the staple line reinforcement (SLR) in LSG, the conclusions were inconsistent regarding effectiveness. This article aims to discuss effectiveness of oversewing the staple line in LSG. Methods: From the start date of each database to September 27, 2018, a comprehensive search of published articles in English was conducted in PubMed, Embase, Central (Cochrane) databases and Scopus databases. We extracted and analyzed the main results on postoperative bleeding, staple line leakage, hospital stay and operative time of the final included articles. This review was compliant with PRISMA guidelines. Results: Finally, we extracted and analyzed 11 randomized controlled trials (RCTs) which contain 2411 patients (1219 patients as part of the oversewing (OS) group and 1192 patients in the no-oversewing (NOS) group). In the OS group, there were 15 cases (1.23%) of postoperative bleeding, and 8 cases (0.66%) of postoperative leakage. While in the NOS group, 35 patients (2.94%) had postoperative bleeding and 21 patients (1.76%) had postoperative leakage. By comparing and analyzing the OS group and the NOS group, the risk ratio (RR) for postoperative bleeding was 0.48 (95% confidence interval [CI], 0.27-0.83 p = 0.447). In addition, the RR for postoperative leakage was 0.44 (95% CI, 0.21-0.89 p = 0.835). The standardized mean difference (SMD) for hospital stay was -0.10 (95% CI, -0.25 to 0.04 p = 0.061) and 2.26 for operative time (95%CI, 0.82-3.69 p = 0.000). Conclusion: This study suggested that oversewing the staple line during LSG has a significant clinical value: it decreased the incidence of postoperative bleeding, postoperative leakage; moreover, it also significantly prolonged the operative time and but did not change hospital stay. More high-quality and large sample RCTs are expected to get more accurate results.

Clinical Outcomes of Sleeve Gastrectomy Versus Roux-En-Y Gastric Bypass After Failed Adjustable Gastric Banding.

BACKGROUND: Over recent decades, laparoscopic adjustable gastric banding (LAGB) has been among the most common bariatric surgeries. Nowadays, many patients require revision surgery due to insufficient weight loss and band-related complications. Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are the two most common revision surgeries for failed LAGB, but the conclusions about their efficacy and safety have been inconsistent. This meta-analysis aimed to review the clinical outcomes of SG and RYGB after failed LAGB. METHODS: In accordance with the PRISMA guidelines, the PubMed, Embase, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were systematically searched for articles that had studied the efficacy and safety of SG and RYGB. The most appropriate effects model was chosen based on the heterogeneity of the articles included in this meta-analysis. Statistical analysis was conducted using Stata 14.0. RESULTS: Of 586 articles that were retrieved, 16 articles which examined 2141 SG and 2990 RYGB patients met the inclusion criteria. The patients in RYGB groups showed increased percent excess weight loss (%EWL) at 12 and 24 months after revision surgery but no statistically significant change was found about %EWL after 3, 6, or 36 months. In addition, RYGB was associated with a higher rate of complications, interventions, and readmission in addition to being of more operative time. CONCLUSIONS: This review suggested that RYGB was more effective at demonstrating weight loss after 12 and 24 months, but comparisons of the long-term efficacy of RYGB with that of SG remain inconclusive. In addition, RYGB was accompanied by a greater number of post-operative complications, interventions, and readmissions. Thus, surgeons should consider the overall status of the patients and their comorbidities as crucial factors when selecting a form of revision surgery. Additional high-quality randomized controlled studies are required to further compare the efficacy and safety of these treatments with longer follow-up times.

Differential composition of gut microbiota among healthy volunteers, morbidly obese patients and post-bariatric surgery patients.

The modulation of the gut microbiota was recently deemed one of the mechanisms responsible for the excellent outcomes of bariatric surgery. However, to date, only few studies have assessed this, and they have high heterogeneity. In the present study, next-generation 16S ribosomal DNA amplicon sequencing was used to characterize the gut microbiota of healthy volunteers, as well as patients prior to and after sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB). Significant differences in α diversity, ß diversity and species were identified between the different groups/time-points. The results demonstrated excellent outcomes of SG and RYGB. The ß diversity was lower in healthy volunteers compared with that in morbidly obese patients with or without type 2 diabetes mellitus. At 3 months after SG, the α diversity was increased and the ß diversity was decreased. The abundance of certain species changed significantly after SG and RYGB. It was also revealed that the abundance of certain microbes was significantly correlated with the body mass index, fasting blood glucose and glycosylated haemoglobin. It may be concluded that bariatric surgery may cause obvious alterations in the gut microbiota and compared with healthy volunteers and obese patients without bariatric surgery, the microbiota composition of post-bariatric surgery has unique characteristics. However, studies with a larger cohort and longer follow-up may be required to confirm these results.

Comparison of anastomotic leakage rate and reoperation rate between transanal tube placement and defunctioning stoma after anterior resection: A network meta-analysis of clinical data.

OBJECTIVE: Defunctioning stoma (DS) and transanal tube (TT) placement have all been reported to be effective procedures to prevent anastomotic leakage after anterior resection. However, there are few studies that directly compare the 2 procedures, and those that do are unclear. METHODS: We performed a systematic literature search from the databases of Pubmed, Embase and Cochrane library. We limited the publication date from 2008/01/01 to 2018/07/29. The bias risk of eligible randomized controlled trials and cohort studies were assessed by Cochrane Collaboration's tool and Newcastle-Ottawa Scale, respectively. The direct meta-analysis was performed by RevMan 5.3 software. The network graph, inconsistency test and comparison-adjusted funnel plot were performed by the Stata 14.0 software. The indirect meta-analysis and rank probabilities were performed by GeMTC R package. RESULTS: 6 randomized controlled trials and 26 cohort studies were included in our meta-analysis. All eligible studies were assessed as low risk of bias. The anastomotic leakage rate and reoperation rate was lower in the patients receiving DS or TT placement than patients with non-protection. DS shared similar anastomotic leakage rate with TT. However, the reoperation rate was significantly lower in patients receiving DS than patients receiving TT. CONCLUSION: Both TT and DS were protective factors for anastomotic leakage after anterior resection for rectal cancer. DS reduced severity of anastomotic leakage in a more effective way than TT placement. However, we still suggested the routing use of TT for decreasing the risk of anastomotic leakage in anterior resection because it was cheaper and technically simpler.

Outcomes of transanal tube placement in anterior resection: A meta-analysis and systematic review.

BACKGROUND: In recent years, transanal tube placement was reported to be an effective procedure preventing anastomotic leakage after anterior resection of rectal cancer. However, this procedure is still controversial owing to inconsistent results found in previous studies. METHODS: A comprehensive literature search was performed using Pubmed, Embase, Cochrane library from the databases inception up until June 21, 2018. The methodological quality of randomized controlled trials and cohort studies were evaluated by Cochrane Collaboration's tool for assessing risk of bias and Newcastle-Ottawa Scale, respectively. Statistical analysis was performed using the RevMan 5.3 software. RESULTS: 1 randomized controlled trial and 9 cohort studies were included in our meta-analysis. The randomized controlled trial was proven to be low risk according to the Cochrane Collaboration's tool for assessing risk of bias. All of the cohort studies proved a high quality according to the Newcastle-Ottawa Scale. Patients in transanal tube group had more disadvantageous preoperative demographic characteristics than patients in non-transanal tube group. The anastomotic leak rate was lower in the transanal tube group. Patients in the transanal tube group tended to have lower reoperation rates and shorter hospital stays compared with patients in the non-transanal tube group. CONCLUSION: Despite various unfavorable preoperative characteristics, anastomotic leakage after anterior resection was lower in patients who received transanal tube placement compared with the control group. Transanal tube placement may be an alternative procedure of defunctioning stoma. A large sample size, multicenter RCT was needed to prove our results.

Outcomes of Mini vs Roux-en-Y gastric bypass: A meta-analysis and systematic review.

BACKGROUND: Mini gastric bypass has been proved to be capable of achieving excellent metabolic results by numerous published studies. Compared to Roux-en-Y gastric bypass, mini gastric bypass is a technically simpler and reversible procedure. However, comparative outcomes of the effectiveness between Mini gastric bypass and Roux-en-Y gastric bypass remain unclear. METHODS: A systematic literature search was performed in Pubmed, Embase, Cochrane library from inception to February 9, 2018. For assessment of method quality, NOS (Newcastle-Ottawa Scale) and Cochrane Collaboration's tool for assessing risk of bias were used for cohort study and randomized controlled trials, respectively. The meta-analysis was performed by RevMan 5.3 software. RESULTS: 10 cohort studies and 1 randomized controlled trial was included in our meta-analysis. The method quality of the 10 cohort studies was proved as high quality according to the Newcastle-Ottawa Scale. The randomized controlled trial was proved to have a low risk of bias according to Cochrane Collaboration's assessment. Patients receiving mini-gastric bypass had multiple advantageous indexes as compared with patients receiving Roux-en-Y gastric bypass. Examples include: a higher 1-year EWL% (P < 0.05), higher 2-year EWL% (P < 0.05), higher type 2 diabetes mellitus remission rate, as well as a shorter operation time (P < 0.05). No significant statistical difference was observed in hypertension remission rate, mortality, leakage rate, GERD rate, or hospital stay between mini gastric bypass and Roux-en-Y gastric bypass. CONCLUSION: Mini gastric bypass seems to be a simpler procedure with a better weight reduction effect. This seems to also be the case regarding remission rates of type 2 diabetes mellitus when using Mini gastric bypass in comparison to Roux-en-Y gastric bypass. A small sample size and biased data may have influenced the stability of our results. In light of this, surgeons should treat our results in a conservative way. Larger sample size and multi-center randomized control trials are needed to compare the effectiveness and safety between mini-gastric bypass and Roux-en-Y gastric bypass.

Comparison of safety and effectiveness between laparoscopic mini-gastric bypass and laparoscopic sleeve gastrectomy: A meta-analysis and systematic review.

BACKGROUND: The laparoscopic mini-gastric bypass is a newly emerged surgical procedure in recent years. Owe to safe and simple process and effective outcomes, laparoscopic mini-gastric bypass has quickly become one of the most popular procedures in some countries. The safety and effectiveness of laparoscopic mini-gastric bypass versus laparoscopic sleeve gastrectomy remain unclear. METHODS: A systematic literature search was performed in PubMed, Embase, Cochrane library from inception to May 20, 2017. The methodological quality of Randomized Controlled Trials and non-Randomized Controlled Trials were, respectively, assessed by Cochrane Collaboration's tool for assessing risk of bias and Newcastle-Ottawa scale. The meta-analysis was performed by RevMan 5.3 software. RESULTS: Patients receiving mini-gastric bypass had a lot of advantageous indexes than patients receiving sleeve gastrectomy, such as higher 1-year EWL% (excess weight loss), higher 5-year EWL%, higher T2DM remission rate, higher hypertension remission rate, higher obstructive sleep apnea (OSA) remission rate, lower osteoarthritis remission rate, lower leakage rate, lower overall late complications rate, higher ulcer rate, lower gastroesophageal reflux disease (GERD) rate, shorter hospital stay and lower revision rate. No significant statistical difference was observed on overall early complications rate, bleed rate, vomiting rate, anemia rate, and operation time between mini-gastric bypass and sleeve gastrectomy. CONCLUSION: Mini-gastric bypass is a simpler, safer, and more effective bariatric procedure than laparoscopic sleeve gastrectomy. Due to the biased data, small sample size and short follow-up time, our results may be unreliable. Large sample and multicenter RCT is needed to compare the effectiveness and safety between mini-gastric bypass and sleeve gastrectomy. Future study should also focus on bile reflux, remnant gastric cancer, and long term effectiveness of mini-gastric bypass.

Effect of Roux-en-Y gastric bypass surgery on intestinal Akkermansia muciniphila.

AIM: To investigated changes in intestinal Akkermansia muciniphila (A. muciniphila) and explored the mechanism underlying the therapeutic effects of Roux-en-Y gastric bypass (RYGB) surgery on type 2 diabetes in diabetic Goto-Kakizaki (GK) rats. METHODS: Male diabetic GK rats (n = 12) aged 8 wk were randomly assigned to the surgery group (GK-RYGB) or sham surgery group (GK-Sham) (n = 6 per group), and another 6 male Wistar rats aged 8 wk served as controls (WS-Sham). In the surgery group, RYGB surgery was conducted, and a sham operation was performed in both sham groups. Fasting blood glucose (FBG) levels before and after surgery, fasting levels of serum insulin and serum glucagon-like peptide-1 (GLP-1) and levels 30 min after intragastric injection of glucose, and the amount of A. muciniphila in the stool were determined. Insulin and GLP-1 were measured by enzyme-linked immunosorbent assay, and A. muciniphila were detected by fluorescence-based quantitative polymerase chain reaction. RESULTS: The FBG was improved, and serum GLP-1 and insulin increased significantly (P < 0.05) in the GK-RYGB group after surgery compared to levels before surgery and to levels in the GK-Sham group. Before surgery, the amounts of A. muciniphila in the GK-RYGB and GK-Sham groups were significantly lower than in the WS-Sham group (P < 0.05). After surgery, the amount of A. muciniphila in the GK-RYGB group increased markedly compared to that before surgery and to that in the GK-Sham and WS-Sham groups (P < 0.05). In addition, the A. muciniphila amount was positively related to GLP-1 (r = 0.86, P < 0.05). CONCLUSION: Our results demonstrated RYGB surgery may increase GLP-1 secretion, elevate serum insulin after intragastric injection of glucose, and improve insulin resistance in diabetic GK rats, thereby contributing to a significant reduction in blood glucose. The increased amount of A. muciniphila after RYGB surgery may be related to elevated GLP-1 secretion.

The correlation between EGFR mutation status and the risk of brain metastasis in patients with lung adenocarcinoma.

To explore the correlation between epidermal growth factor receptor (EGFR) mutation status and the risk of brain metastasis (BM) in patients with lung adenocarcinoma, the clinical data of 100 patients with pathologically confirmed lung adenocarcinoma and known EGFR mutation status at exon 18, 19, 20, or 21 were analyzed retrospectively. The incidence of BM was similar between patients with wild-type EGFR and those with EGFR mutations (p = 0.48). However, among patients with EGFR mutations, the incidence of BM was significantly higher in patients with mutation at exon 19 than in patients with mutation at other sites (p = 0.007). Besides, among patients with heterochronous BM, 66.7 % had EGFR mutations. Regarding brain-metastasis-free survival (BMFS), patients with EGFR sensitive mutations (mutation at exon 19/21/and dual mutation) had significantly shorter BMFS compared with patients with wild-type EGFR (p = 0.018). For patients treated only with chemotherapy, BM was an unfavorable prognostic factor. Patients with BM had worse overall survival compared with those without BM (p = 0.035). However, in patients with BM and EGFR sensitive mutations, those treated with tyrosine kinase inhibitors (TKIs) had significantly longer overall survival compared with those treated with chemotherapy only (p = 0.0081). In conclusion, among patients with EGFR mutations, those mutated at exon 19 had the highest incidence of BM. Furthermore, patients with EGFR mutations are more likely to develop heterochronous BM. The BMFS was significantly shorter in patients with EGFR sensitive mutations. TKIs improved the survival of patients with lung adenocarcinoma and BM who harbored EGFR sensitive mutations.

[The effects of gastric bypass procedures on blood glucose, gastric inhibitory polypeptide and glucagon-like peptide-1 of normal glucose tolerance dogs].

OBJECTIVE: To observe postoperative glucose tolerance, gastric inhibitory polypeptide (GIP) , and glucogan-like peptide-1 (GLP-1) in normal glucose level dogs after undergoing gastric bypass procedures, and to explore the mechanism of gastric bypass procedures to treat type 2 diabetes. METHODS: The 6 dogs with normal glucose tolerance had undergone gastric bypass procedures, and measure preoperative and postoperative oral and intravenous glucose tolerance (at time points 1, 2, and 4 weeks) through changes in blood glucose, insulin, gastric inhibitory polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and measure preoperative and postoperative week 4 pancreatic tissue morphology. RESULTS: Second weeks after operation, the fasting blood sugar was (3.58 ± 0.33) mmol/L, and significantly lower than preoperative (t = 3.571, P < 0.05). The GLP-1 level before oral glucose tolerance test (OGTT) and 30 minutes after OGTT were (0.90 ± 0.21) and (0.91 ± 0.19) pmol/L respectively, and significantly higher than preoperative (t value were -3.660 and -2.971, P < 0.05). GLP-1 levels began to decrease in the second week after surgery. After 4 weeks, the index recovered to the preoperative level. Four weeks after surgery when compared with preoperative, islet morphology, islet number (6.8 ± 0.8 and 7.1 ± 0.8 respectively) and islet cells (16.7 ± 2.5 and 16.3 ± 3.1 respectively) did not change significantly (P > 0.05). CONCLUSION: Gastric bypass procedures could be briefly affect normal glucose tolerance in dogs' blood glucose, insulin and diabetes-related gastrointestinal hormones.

[Application of side to side anastomosis between the lesser curvature of stomach and jejunum in laparoscopic Roux-en-Y gastric bypass].

OBJECTIVE: To evaluate the application of side-to-side anastomosis of the lesser curvature of stomach and jejunum in laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS: Clinical data of 29 patients with type 2 diabetes mellitus (T2DM) undergoing side to side anastomosis of the lesser curvature of stomach and jejunum in LRYGB from May 2012 to November 2012 in Department of General Surgery, Beijing Tiantan Hospital, Capital Medical University were analyzed retrospectively. RESULTS: All the procedures were successfully completed without conversion to laparotomy. The side-to-side anastomosis of the lesser curvature of stomach and jejunum avoided the laparoscopic suture. No gastrojejunostomy anastomotic bleeding, fistula, obstruction and other complications occurred after operation and no complications of gastrojejunostomy anastomosis were found during a follow up of 1 to 7 months. CONCLUSIONS: Side-to-side anastomosis of the lesser curvature of stomach and jejunum in LRYGB can manipulate the size of anastomosis accurately and avoid the laparoscopic suturing. It is simple and easy to learn.

S100A4 siRNA inhibits human pancreatic cancer cell invasion in vitro.

OBJECTIVE: Pancreatic cancer is one of the most deadly cancers, which is characterized by its high metastatic potential. S100A4 is a major prometastatic protein involved in tumor invasion and metastasis which precise role in pancreatic cancer has not been fully investigated. We knocked down the S100A4 gene in the Bxpc-3 pancreatic cancer cell line via RNA interference to study the changes in cell behavior. METHODS: Real-time polymerase chain reaction and western blotting were used to detect mRNA and protein expression levels of S100A4, matrix metalloproteinase (MMP)-2, E-cadherin and thrombospondin (TSP)-1. Transwell chambers were used to detect the migration and invasion abilities; a cell adhesion assay was used to detect adhesion ability; colony forming efficiency was used to detect cell proliferation; flow cytometry was used to detect apoptosis. RESULTS: S100A4 mRNA expression was reduced to 17% after transfection with S100A4-siRNA, and protein expression had a similar trend. mRNA and protein expression of MMP-2 was reduced and that of E-cadherin and TSP-1 was elevated, indicating that S100A4 affects their expression. S100A4-silenced cells exhibited a marked decrease in migration and invasiveness and increased adhesion, whereas overall proliferation and apoptosis were not overtly altered. CONCLUSION: S100A4 and its downstream factors play important roles in pancreatic cancer invasion, and silencing A100A4 can significantly contain the invasiveness of pancreatic cancer.

Knockdown of Ezrin by RNA interference reverses malignant behavior of human pancreatic cancer cells in vitro.

BACKGROUND: Pancreatic cancer is one of the most aggressive tumors with a dismal prognosis. The membrane cytoskeletal crosslinker Ezrin participates in several functions including cell proliferation, adhesion, motility and survival. There is increasing evidence that Ezrin is overexpressed in vast majority of malignant tumors and regulates tumor progression. However, its roles in pancreatic cancer remain elusive. METHODS: Three pairs of specific Ezrin siRNAs were designed and synthetized and screened to determine the most efficient one for construction of a hairpin RNA plasmid targeting Ezrin. After transfection into the Panc-1 pancreatic cancer cell line, real-time quantitative PCR and Western blotting were performed to examine the expression of mRNA and protein. The MTT method was applied to examine the proliferation and the drug sensibility to Gemcitabine. Flow cytometry was used to assess the cycle and apoptosis, while capacity for invasion was determined with transwell chambers. Furthermore, we detected phosphorylated-Erk1/2 protein and phosphorylated-Akt protein by Western blotting. RESULTS: Real-time quantitative PCR and Western blotting revealed that Ezrin expression was notably down-regulated at both mRNA and protein levels by RNA interference (P< 0.01). Proliferation was inhibited and drug resistance to gemcitabine was improved (P< 0.05). Flow cytometry showed that the proportion of cells in the G1/G0 phase increased (P< 0.01), and in G2/M and S phases decreased (P< 0.05), with no apparent differences in apoptosis (P> 0.05). The capacity for invasion was markedly reduced (P< 0.01). In addition, down-regulating Ezrin expression had no effect on phosphorylated-Akt protein (P>0.05), but could decrease the level of phosphorylated-Erk1/2 protein (P< 0.05). CONCLUSIONS: RNA interference of Ezrin could inhibit its expression in the pancreatic cancer cells line Panc-1, leading to a potent suppression of malignant behavior in vitro. Assessment of potential as a target for pancreatic cancer treatment is clearly warranted.

Knockdown of radixin by RNA interference suppresses the growth of human pancreatic cancer cells in vitro and in vivo.

Radixin, encoded by a gene on chromosome 11, plays important roles in cell motility, invasion and tumor progression. However, its function in pancreatic cancer remains elusive. In this study, radixin gene expression was suppressed with a lentivirus-mediated short-hairpin RNA (shRNA) method. We found that radixin shRNA caused down-regulation of radixin in PANC-1 cells, associated with inhibition of pancreatic cancer cell proliferation, survival, adhesion and invasive potential in vitro. When radixin-silenced cells were implanted in nude mice, tumor growth and microvessel density were significantly inhibited as compared to blank control cells or nonsense shRNA control cells. Thrombospondin-1 (TSP-1) and E-cadherin were up-regulated in radixin-silenced PANC-1 cells. Our results suggest that radixin might play a critical role in pancreatic cancer progression, possibly through involvement of down-regulation of TSP-1 and E-cadherin expression.

Regulation of estrogen receptors alpha and beta in human breast carcinoma by exogenous leptin in nude mouse xenograft model.

BACKGROUND: It is essential to clarify the interactions of hormones during the progression of human breast cancer. This study examined the effects of exogenous human leptin on estrogen receptor (ER) alpha and beta in human breast tumor tissue in a nude mouse xenograft model. METHODS: We created nude mice xenografts of MCF-7 human breast cancer cells, and randomly divided them into an experimental group and a control group. The mice in experimental group were injected subcutaneously around tumors with human leptin, while the control group were injected with the same dose of normal saline. A real-time RT-PCR assay was developed to quantify the mRNA of ERalpha, beta in the tumor tissues. Western blotting analyses were used to assess the relative quantities of the ERalpha, beta proteins. RESULTS: Leptin-treated xenografted nude mice were successfully established. The amount of ERalpha mRNA was significantly higher in the leptin group than in the control group (P < 0.01), while the amount of ERbeta mRNA was significantly lower in the leptin group than in the control group (P < 0.01). Western blotting analyses revealed that the ERalpha protein level was significantly higher in the leptin group than in the control group (P < 0.01), while the ERbeta protein level was significantly lower in the leptin group than in the control group (P < 0.01). CONCLUSIONS: Nude mouse xenograft model can be safely and serviceably treated with human leptin by subcutaneous injections around tumor. ERalpha, beta were both targets of leptin in breast cancer. Leptin can up-regulate the expression of ERalpha and down-regulate the expression of the ERbeta in human breast tumor.

A crucial role of nitric oxide in acute lung injury secondary to the acute necrotizing pancreatitis.

To investigate the role of nitric oxide (NO) in acute lung inflammation and injury secondary to acute necrotizing pancreatitis (ANP), 5% sodium taurocholate was retrogradely injected into the biliopancreatic duct of rats to ANP model. These ANP rats were given L-Arginine (L-Arg, 100 mg/kg), L-NAME (10 mg/kg), or their combination by intraperitoneal injection 30 min prior to ANP induction. At 1, 3, 6, and 12 hours after ANP induction, lung NO production, and inducible NO synthase (iNOS) expression were measured. Lung histopathological changes, bronchoalveolar lavage (BAL) protein concentration, proinflammatory mediators tumor necrotic factor alpha (TNF-alpha), and lung tissue myeloperoxidase (MPO) activity were examined. Results showed that NO production and iNOS mRNA expression in alveolar macrophages (AMs) were significantly increased along with significant increases in lung histological abnormalities and BAL proteins in the ANP group, all of which were further enhanced by pretreatment with L-Arg and attenuated by pretreatment with L-NAME, respectively. These markers were slightly attenuated by pretreatment with combination of L-Arg + L-NAME, suggesting that NO is required for initiating the acute lung damage in ANP rats, and also that L-Arg-enhanced lung injury is mediated by its NO generation rather than its direct effect. MPO activity and TNF-alpha expression in lung were upregulated in the ANP rats and further enhanced by pretreatment with L-Arg and attenuated by pretreatment with L-NAME, respectively. These results suggest that overproduction of NO mediated by iNOS in the lung is required for the acute lung inflammation and damage secondary to ANP.

Suppression of matrix metalloproteinase-2 via RNA interference inhibits pancreatic carcinoma cell invasiveness and adhesion.

AIM: To investigate the inhibitory effects of RNA interference (RNAi) on expression of matrix metalloproteinase-2 (MMP-2) gene and invasiveness and adhesion of human pancreatic cancer cell line, BxPC-3. METHODS: RNAi was performed using the vector (pGPU6)-based small interference RNA (siRNA) plasmid gene silence system to specifically knock down MMP-2 expression in pancreatic cancer cell line, BxPC-3. Four groups of different specific target sequence in coding region of MMP-2 and one non-specific sequence were chosen to construct four experimental siRNA plasmids of pGPU6-1, pGPU6-2, pGPU6-3 and pGPU6-4, and one negative control siRNA plasmid of pGPU6 (-). MMP-2 expression was measured by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Cell proliferation and apoptosis were examined by methyl thiazolyl tetrazolium (MTT) and flow cytometry, respectively. The abilities of adhesion and invasion were detected by cell adhesion assay and cell invasion assay using Transwell chambers. RESULTS: The expression of MMP-2 was inhibited and the inhibitory effects of different sequence varied. pGPU6-1 group had the most efficient inhibitory effect, followed by pGPU6-2 and pGPU6-3 groups. Invasiveness and adhesion were more significantly reduced in pGPU6-1, pGPU6-2 and pGPU6-3 groups as compared with pGPU6 (-) and blank control groups. However, no difference concerning cell proliferation and apoptosis was observed after transfection between experiment groups and control groups. CONCLUSION: RNAi against MMP-2 successfully inhibited the mRNA and protein expression of MMP-2 in the pancreatic cancer cell line, BxPC-3, leading to a potent suppression of tumor cell adhesion and invasion without affecting cell proliferation and apoptosis. These findings suggest that the RNAi approach towards MMP-2 may be an effective therapeutic strategy for the clinical management of pancreatic tumor.

[Comparative study of mesh-plug and polypropylene hernia system tension-free hernioplasty for inguinal hernia].

OBJECTIVE: To compare the effects of mesh-plug and polypropylene hernia system (PHS) tension-free hernioplasty so as to explore the strategy of treatment for different patients. METHODS: Eighty patients with inguinal hernia were assigned into 3 equal groups according to the randomization schedule: PHS group and mesh-plug group. The operating time and the outcomes were recorded. RESULTS: The operating times of the mesh-plug group was 73.8 minutes significantly longer than that of the PHS group (56.5 minutes, P < 0.05). There was no significant difference in the recovery progress between these 2 groups. The numbers of patients who had sense of foreign body and numbness in the mesh-plug group were significantly greater than those in the PHS group (both P < 0.05). CONCLUSIONS: Mesh-plug tension-free hernioplasty is indicated for most inguinal hernia patients owing to the simple operation. More rational in design and more effective in reduction of recurrence, PHS is suitable for thin patients or patients with week or large transversalis fascia defection. And PHS is able to reduce the postoperative discomfort.